Abstract

The ethanolic extract of the roots ofMurraya exotica(Rutaceae) yielded twenty coumarins, including twelve previously undescribed compounds named exoticoumarins A–L (1–12; two biscoumarins, five coumarin hybrids, and five monomers). Their structures, including absolute configurations, were elucidated by a combination of NMR and HR-ESI-MS analyses, single-crystal X-ray diffraction, ECD exciton coupling, Mo2(OAc)4- and Rh2(OCOCF3)4-induced ECD, comparison of experimental with calculated ECD spectra, and chemical hydrolysis. Anti-inflammatory evaluation in LPS-stimulated RAW264.7 macrophages identified exoticoumarins A and K (1and11) as potent inhibitors of nitric oxide (NO) production, with IC50values of 7.41 and 10.63 μM, respectively. Mechanistic studies revealed that1suppressed nitric oxide synthase (iNOS) expression at both transcriptional and translational levels, an effect associated with the inhibition of c-Jun N-terminal kinase (JNK) phosphorylation within the mitogen-activated protein kinase (MAPK) signaling pathways, without markedly affecting extracellular regulated protein kinases (ERK) 1/2 phosphorylation. These findings highlight exoticoumarin A (1) as a promising anti-inflammatory lead derived fromM. exotica.